# Differentiation of tumor progression from radiation necrosis using MR cell size imaging

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $194,304

## Abstract

PROJECT SUMMARY
This R21 proposal seeks to develop a cell-size-based MRI technique, Selective Size MR Imaging using Filters
via diffusion Times (SSIFT), as a novel approach for imaging brain metastases (BM) in patients with high
specificity, and to evaluate its potential to differentiate recurrent BM from radiation necrosis (RN) induced by
stereotactic radiosurgery (SRS). Approximately 10–30% of all cancer patients will eventually develop BM in
their lifetime, and SRS is a common treatment for patients with BM to improve the local control. However,
about 10-20% of treated BM will eventually develop new contrast-enhancing lesions that are either RN or
recurrent BM. These two types of lesions usually occur within a similar time frame but need to be treated
differently: RN can be managed conservatively to alleviate symptoms; by contrast, tumor recurrence is often
managed with surgery or further radiation to control tumor progression. Unfortunately, RN is indistinguishable
from tumor recurrence on standard-of-care MRI with gadolinium (Gd)-based contrast agents due to the
breakdown of the blood-brain barrier (BBB) in both types of lesions. Therefore, there is a need for clinical
radiation oncology to develop a reliable non-invasive imaging method to differentiate tumor recurrence from
RN. Despite numerous attempts to develop a variety of advanced imaging methods to tackle this clinical
challenge, there is still no single imaging method that has been widely accepted as a reliable imaging
biomarker. We hereby propose a new idea, i.e., to use endogenous information on cell size to differentiate BM
from RN. Different from our previous quantitative cell size MRI with a long scan time, we propose here a fast
SSIFT method that serves as a cell-size-based filter to selectively emphasize signals arising from large cancer
cells with simultaneous suppression of signals from other brain abnormalities, such as RN. We have validated
SSIFT in preclinical animal models to demonstrate its ability to differentiate BM from RN, but it remains unclear
if SSIFT will work in patients with BM. We hereby hypothesize that SSIFT is a practical, reliable, and specific
approach for imaging BM in patients with the capability to differentiate recurrent BM from RN. To test this
hypothesis, we have assembled a multidisciplinary team and propose [Aim 1] to refine a reliable and efficient
SSIFT protocol in imaging BM patients and [Aim 2] to evaluate the clinical ability of SSIFT in differentiating
recurrent BM from RN induced by SRS. Upon completion, the proposed study will break new ground to
establish a new type of cell-size-based MRI technique geared towards addressing an important, common
dilemma in the management of BM patients with SRS treatments. In addition, the ability to differentiate BM
from peri-tumor edema makes this new method another possible alternative imaging approach for BM patients
with kidney dysfunction who are not candidates for gadolinium-agent-based MRI.

## Key facts

- **NIH application ID:** 10791886
- **Project number:** 5R21CA270731-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Junzhong Xu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,304
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791886

## Citation

> US National Institutes of Health, RePORTER application 10791886, Differentiation of tumor progression from radiation necrosis using MR cell size imaging (5R21CA270731-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10791886. Licensed CC0.

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